Process for the preparation of dihydroxy esters and derivatives thereof

Abstract

A process is provided for the preparation of a compound of formula (1) wherein R and R′ represent optionally substituted hydrocarbyl groups and X represents a hydrocarbyl linking group. The process comprises either the stereoselective reduction of the keto group in a dihydroxy keto precursor followed by selective esterification of a primary hydroxy, or selective esterification of a primary hydroxy of a dihydroxy keto precursor followed by stereoselective reduction of the keto group.

1. A process for the preparation of a compound of Formula (5) 
       
         
           
           
               
               
           
         
       
       which comprises:
 a) preparing a compound of Formula (1) 
 
       
         
           
           
               
               
           
         
         b) reacting the compound of Formula (1) with 2,2-dimethoxypropane to form an acetonide; and 
         c) removing the group R′—(C═O)—; 
       
       wherein
 X represents an optionally substituted hydrocarbyl linking group, and 
 R and R′ each independently represent an optionally substituted hydrocarbyl group, and 
 
       wherein the process for preparing the compound of Formula (1) comprises either
 a) the stereoselective reduction of a compound of Formula (2) 
 
       
         
           
           
               
               
           
         
       
       to produce a compound of Formula (3), and 
       
         
           
           
               
               
           
         
         b) esterification of the compound of Formula (3) in the presence of a compound of formula R″—O—COR′ and a lipase or hydrolase enzyme thereby to form the compound of Formula (1); or 
         c) esterification of a compound of Formula (2) in the presence of a compound of formula R″—O—COR′ and a lipase or hydrolase enzyme thereby to form a compound of Formula (4), and 
       
       
         
           
           
               
               
           
         
         d) the stereoselective reduction of the compound of Formula (4) to produce the compound of Formula (1) 
       
       wherein
 X, R and R′ are as defined above, and 
 R″ represents an optionally substituted hydrocarbyl group. 
 
     
     
       2. A process according to  claim 1 , wherein R′ represents an optionally substituted alkyl group. 
     
     
       3. A process according to  claim 1 , wherein X represents a —CH 2 — group. 
     
     
       4. A process according to  claim 1  or  claim 2 , wherein R″ represents a vinyl or isopropenyl group. 
     
     
       5. A process according to  claim 1 , wherein R′ represents a substituted or unsubstituted C 1-6  alkyl group. 
     
     
       6. A process according to  claim 4 , wherein R′ represents a methyl group. 
     
     
       7. A process according to  claim 1 , wherein the compounds of Formulae (2) or (4) are reduced by contact with an organism possessing the properties of a microorganism selected from  Beauveria, Pichia, Candida, Kluyveromyces  or  Torulaspora genera  or an enzyme extracted therefrom. 
     
     
       8. A process according to  claim 1 , wherein the compounds of Formulae (2) or (4) are reduced by contact with an organism selected from the group consisting of  Pichia angusta, Pichia pastoris, Candida guillermondii, Saccharomyces carlsbergensis, Pichia trehalophila, Kluyveromyces drosopliarum  and  Torulospora hansenii , or an enzyme extracted therefrom. 
     
     
       9. A process according to  claim 7  or  claim 8 , wherein whole cells are employed. 
     
     
       10. A process according to  claim 7  or  8 , wherein the compounds of Formulae (2) or (4) are reduced at a pH of from about 4 to about 5. 
     
     
       11. A process according to  claim 1 , wherein the compounds of Formulae (2) or (3) are esterified in the presence of an enzyme selected from the group consisting of  Porcine pancreatic lipase, Candida cylindracea lipase, Pseudomonas fluorescens lipase, Candida antarctica  fraction B and lipase from  Humicola lanuginosa.    
     
     
       12. A process according to  claim 1 , wherein the compound R″—O—COR′ is vinyl acetate. 
     
     
       13. A process according to  claim 1 , wherein the wherein the R′—(C═O)— is removed by treatment with a basic, alcoholic solution.